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. 2019 Feb 28;9:3185. doi: 10.1038/s41598-019-39676-3

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Cytosolic resting calcium (restCa) level in EDL muscle fibers measured by FURA-2 cytofluorimetric technique. RestCa level measured in (A) 130 days-old SOD1^G93A animals and in (B) 140 days-old MLC/SOD1^G93A animals. *Significantly different with respect to WT animals (P < 0.05 by Unpaired Student t-test). (C) Representative traces showing a 40 mM caffeine-induced increase of restCa in WT (black trace) and in SOD1^G93A (gray trace) mice. (D) Correspondent barplot constructed using the mean values ± S.E.M. obtained from 15–20 fibers. (E) Schematic representation of the decreased expression of RyR1 and SERCA1 mRNA (black arrows) responsible for the cytosolic calcium increase. Although the decreased expression of RyR in SOD1 ^G93A may indicate the reduction of Ca flux from SR to the cytosol, SERCA reduction slow down the reuptake in the SR. Slight modification in restCa level were observed in MLC/SOD1^G93A animals in line with the lack of changes in RyR and SERCA expression.